Reduction of imines and reductive amination reactions are commonly employed in the chemical field to produce amines. For instance, reductive amination reactions are widely used in the synthesis of pharmaceutical compounds and their intermediates. Typically, reductive amination of an aldehyde or ketone involves their reaction with either ammonia, a primary amine, or secondary amine under reductive conditions to respectively yield corresponding primary, secondary, or tertiary amines.
Reducing agents such as NaBH3CN, NaBH(OAc)3, and boranes (e.g. pyridine borane) are commonly used to provide the reductive conditions required in the reductive amination process. However, for successful reductive aminations, a significant excess of NaBH3CN is often required for the reactions to reach completion within a reasonable timeframe. NaBH3CN gives rise to slow reactions, particularly where aromatic ketones and weakly basic amines are used, and final products are often contaminated with highly toxic cyanide. Moreover, NaBH3CN is itself highly toxic and leads to the evolution of toxic byproducts such as HCN and NaCN during post-reaction workups. NaBH(OAc)3 again needs to be used in excessive quantities and is poorly soluble in most commonly used organic solvents. Pyridine borane, on the other hand, can be unsafe to use on industrial scales due to its propensity to violently decompose.
More recently, certain cyclometalated Iridium complexes have been developed to address some of the problems of the prior art (Xiao J et al, Angew. Chem. Int. Ed., 2010, 49: 7548-7552). However, these catalysts, though suitable for use under certain conditions, are not necessarily appropriate for all reductive amination reaction conditions. In order to meet particular synthetic requirements, reaction conditions (e.g. solvents, temperature, pH, etc.) may need to be tailored to the reagents or products of the reductive amination process rather than the catalyst. As such, it is an object of the invention to provide alternative catalysts which meet particular synthetic needs that the prior art catalysts fail to address.